Craniofacial microsomia (CFM) is among the most common craniofacial anomalies. The disorder involves the asymmetric underdevelopment of facial skeletal bones and soft tissue, typically affecting the jaw and ear. CFM usually impairs basic functions such as hearing, speech, respiration, and/or chewing, in addition to its aesthetic effects. It can be life-threatening due to airway compromise. Treatment often requires multiple complex surgical interventions. Almost nothing is known about what causes CFM. Animal models have demonstrated a relationship between the features of CFM and disruption of the vessel that feeds the developing craniofacial structures. The only large epidemiologic study of CFM showed associations with maternal exposures that influence the risk of bleeding or clotting, such as pregnancy pseudoephedrine use and cigarette smoking. We propose to test the "vascular disruption" hypothesis by conducting two data- linkage case-control studies using existing database resources. First, lacking an ICD-9 code specific to CFM, we will identify CFM cases through patient databases at Children's Hospital and Regional Medical Center. We will randomly select controls from among live births in Washington State. Using the Washington State birth certificate and hospital discharge databases, we will ascertain information on factors that are associated with infants' and mothers' risk of bleeding or clotting. We will compare their distribution among cases and controls. The second study differs from the first in that 1) we will ascertain cases directly from the Washington State databases, and 2) cases will be infants diagnosised with underdeveloped ears, the mildest expression of CFM. Using birth certificate data may obviate biases potentially arising in retrospectively conducted interviews of mothers. The relative completeness of Washington State birth certificates and the routine linkage to birth hospital discharge data offer unique resources for the conduct of these analyses. They will allow us to evaluate other potential risk factors not easily ascertained through interviews. This research will be among the first epidemiologic studies of CFM and the first to use linked birth certificates and hospital discharge data. Vascular disruption is widely cited as causing CFM, despite the lack of epidemiologic data that address this claim or CFM more generally. The proposed research addresses this gap in knowledge and could lead to the development of interventions that reduce CFM incidence. [unreadable] [unreadable] [unreadable]